Halogen derivatives of alpha-ethyl propyl cresols



Patented Feb. 23, 1937 ATENT OFFICE HALOGEN DERIVATIVES OF oc-ETHYL PROPYL CRESOLS George W. Raiziss and Le Roy W. Clerncnce, Philadelphia, Pa., assigno North Chicago, 11]., a

rs to Abbott Laboratories,

corporation of Illinois No Drawing. Application June 22, 1934, Serial No. 731,894

6 Claims.

Our invention relates tonew halogen derivatives of a-ethyl propyl cresols, which derivatives we have prepared and have been found by us to possess surprisingly high germicidal values and low toxicity, the germicidal power thereof exceeding the corresponding non-halogen compounds. Our new compounds are of considerable value to the medical profession as bactericidal and bacteriostatic agents.

10 The compounds described below, all of which We have prepared, include monochloro, dichloro, monobromo, and dibromo derivatives of the a-ethyl propyl cresols. The unhalogenated alkyl 15 cresols herein referred to may be prepared as described in our co-pending application, Serial No. 731,898, filed June 22, 1934.

Briefly, this method comprises heating the particular alcohol with zinc chloride to the specific reaction temperature and then slowly adding the desired cresol; maintaining the reaction temperature until the reaction is complete and then pouring the mixture into acidified water. The alkylated cresol which separates is washed with water and extracted with alkali, the alkaline extract in turn being extracted with petroleum ether. The alkyl cresol is separated from its alkaline solution by acidifying with 1101, the desired product being again Washed and distilled in vacuo.

' EXAMPLE 1 Monochloro (at-ethyl propyl) ortho-cresol (iJHa CnHi CHr-CHz-OH Cl 27 grams of sulfuryl chloride are added slowly 40 to 36 grams of a-ethyl propyl ortho-cresol in a flask fitted with a dropping funnel and reflux condenser. Warming on a water bath is sometimes necessary to start the reaction. After the addition of the chloride is complete and there is 45 no further evolution of hydrogen chloride or sulfur dioxide, we warm on water bath for several hours to drive off the last traces to HCl and S02. The mixture is then added to 200 cc. of water. The oily layer which separates is dissolved in 400 cc. 50 of normal sodium hydroxide solution, the insoluble material extracted with petroleum ether, and the clear alkaline solution acidified with hydrochloric acid. The oil which separates is Washed with water and taken up in ether. The

55 ether solution is dried over sodium sulphate, filtered, the ether distilled off, and the residue distilled under vacuum.

The monochloro (ct-ethyl propyl) ortho-cresol boils at 138-140 C. at 14 mm. pressure and has a specific gravity of 1.060. It is a colorless oil, insoluble in water, soluble in organic solvents and dilute alkali.

EXAMPLE 2 Monochloro (or-ethyl propyl) meta-cresol This compound is prepared in exactly the same manner as the previous compound, substituting u-ethyl propyl meta-cresol for the ortho derivative. This compound boils at 141-148 C. at mm. pressure and has a specific gravity of 1.09. It is a colorless oil, soluble in dilute alkali and, organicsolvents, insoluble in water.

EXAMPLE 3 Monochloro (or-ethyl propyl) para-cresol CgH c1- oH-cmom Dichloro (cc-ethyl propyl) ortho-cresol This compound is prepared by the method of Example 1 except that 58 grams of sulfuryl chloride are used. The product boils at 142-148 C.

at 14 mm. pressure and has a specific gravity of 1.144. It is a yellowish oil, soluble in organic solvents and dilute alkali, insoluble in water.

EXAMPLE 5 5 Dz'chloro (ct-ethyl propyl) meta cresol CH 25 OH This compound is prepared the same as in 5 Example 4 except for the substitution of u-ethyl propyl meta-cresol. It has a boiling point of 160-170 C. at 8 mm. pressure and has a specific gravity of 1.165.

EXAMPLE6 Dichloro (ix-ethyl propyl) para-cresol 7 c1- err-cmcm CzHs OH This compound is prepared as in Example 4,

substituting u-ethyl propyl para-cresol. It has a boiling point of 145-153 C. at 10 mm. pressure and a specific gravity of 1.176.

EXAMPLE 7 Monobromo (ix-ethyl propyl) ortho cresol 18 grams of a-ethyl propyl ortho-cresol are dissolved in cc. of chloroform in a flask fitted with a dropping funnel and a reflux condenser. To this is added a little iron powder and then through the funnel is gradually added 16 grams of bromine 'dissolvedzin'zflcc.-of chloroform. It may be necessary to warm the mixture on a water bath to start the reaction. After all the bromine solution is added, the mixture is warmed for one hour. The mixture is then poured into 200 cc. water and the chloroform layer washed with water. We then separate and distill off the chloroform. The residue is dissolved in 200 cc. of normal sodium hydroxide solution and the insoluble portionextracted with petroleum ether.

The clear alkaline portion is acidified and the separated oil is extracted with ether. The ether solution is dried over sodium sulfate and filtered; the ether is distilled ofi and the residue distilled under vacuum. It boils at 154-156 C. at 20 mm. pressure and has a specific gravity of 1.268. It is a pale yellowish oil, insoluble in water, soluble in organic solvents and dilute alkali.

EXAMPIE 8 Monobromo (it-ethyl propyl) meta-cresol cat-caper:

This product is prepared as in the previous example, substituting a-ethyl propyl meta-cresol.

,It has a boiling point of l50156 C. at 8 mm.

pressure and a specific gravity of 1.268. It is a colorless oil, insoluble in water, soluble in dilute 5 alkali and organic solvents.

EXAMPLE 9 Monobromo (or-ethyl propyl) para cvesol 10 02115 Br- OH-CHzOHa 15 This compound is prepared as in Example 7,

substituting u-ethyl propyl para-cresol- It boils 20 at 148-153 C. at 10 mm. pressure and has a specific gravity of 1.249. It is a colorless oil, insoluble in water, soluble in organic solvents and dilute alkali.

EXAMPLE 10 25 Dz'bromo (at-ethyl propyl) ortho-cresol EXAMPLE 11 Dibromo (oz-6th1lJZPTOIJZ/Z) meta cresol 45 OHi This compound boils at 172176 C. at 6 mm. :55 pressure and has a specific gravity of 1.502. It is a yellow oil, insoluble in water, soluble in organic solvents and in dilute alkali.

EXAMPLE 1 2 60 Dibromo (or-ethyl propyl) para-crcsol (llHa Br CH-CHz-CH:

This compound boils at 162-165" C at 10 mm. 70 pressure and has a specific gravity of 1.563. This is a pale yellow oil, insoluble in water, soluble in organic solvents and dilute alkali.

Other halogen derivatives of the a-ethyl 131'013571575 so I cresols, such as those of iodine, may be likewise prepared by analogous methods.

Summarizing as to the properties of the compounds specified above:

Compound B. P. Press. Sp. Gr.

Monochloro (a-ethylpropyl) orthomm.

cresol 138-140 14 1.060 Monochloro (oz-ethyl propyl) metacresol 141-148 10 1.09 Monochloro (oz-ethyl propyl) paracresol 136144 10 1.049 Dichloro (oz-ethyl propyl) ortho-creso1 142148 14 1.144 Diohloro (oz-ethyl propyl) meta-cresol-.. 160-170 8 1.165 Dichloro (oz-ethyl propyDparwcresoL" 145-153 10 1.176 Monobromo (aethyl propyl) orthocresol 154-156 20 1.268 Monobromo (oz-ethyl propyl) metacresol 150-156 8 1.268 Monobromo (a-ethyl propyl) paracresol 148-153" 10 1. 249 Dibromo (a-ethylpropyl) ortho-cresoL. 160-163 10 1.558 20 Dibromo (cm-ethyl propyl) meta-cresoL. 172176 6 1. 502 Dibromo (a-ethylpropyl) paracreso1 162-165 10 1.563

We claim as our invention: 1. A compound having the formula:

(]]H(CzH )-CHz--CH3 i 5 YI wherein R is a cresol nucleus, Y is a halogen, and n is 1 or 2.

2. A compound having the formula:

wherein R is a cresol nucleus, Y is bromine, and n is 1 or 2.

3. A dihalogenated (a-ethyl propyl) cresol. 4. Monobromo (oi-ethyl propyl) meta-cresol. 5. Monobromo (oi-ethyl propyl) ortho-cresol. 6. Dichloro (oi-ethyl propyl) meta-cresol.

GEORGE W. RAIZISS. LE ROY W. CLEMENCE. 

